The goals of this proposal are: 1) to further elucidate the biochemical mechanism of estrogen synthesis as it occurs in placenta, ovary, and nonendocrine fetal and adult tissues, including breast and other solid tumours. Mechanisms which regulate estrogen production at the level of the aromatase enzyme will also be investigated; 2) to investigate the metabolism and mechanism of action of circulating prehormones of both androgen and estrogen in target tissues such as breast and uterus; 3) to study the synthesis, metabolism and possible mechanism of action of steroid hormones during fetal life. Experimental approaches include solubilization of the human placental aromatase and investigation of the component enzymes by classical enzymological techniques. Metabolism of steroids will be studied using radioactive tracers and measurement of enzyme and substrate concentrations. Steroid receptor studies will be carried out using established techniques including charcoal and gel filtration assays and sucrose density ultracentrifugation.